The airway transcriptome as a measure of injury response to and recovery from smoking and alternative tobacco products

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2030-12-31

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https://hdl.handle.net/2144/15237

Abstract

Tobacco smoke remains a major public health concern and a factor contributing to the development and progression of various lung diseases world-wide. Smoking cessation can significantly reduce the risk of developing smoking-related diseases, although some smokers remain at an elevated risk despite quitting. Here, I used high-throughput genomic technologies to pave the way for understanding the transcriptomic response in airway epithelium to tobacco exposure, smoking cessation and potentially reduced exposure products (PREP).
First, using a longitudinal dataset of nasal airway epithelial cells obtained from active smokers enrolled in smoking cessation programs over 24 weeks, I demonstrated that tobacco-related alterations in the airway gene expression are rapidly reversed within 4 to 8 weeks following smoking cessation. Genes with different biological functions revert towards baseline with different dynamics following smoking cessation. These findings suggest that the nasal-epithelium can serve as a minimally-invasive site to measure the reversible impact of smoking.
Secondly, using a dataset of nasal airway epithelial cells from active smokers who switched to potentially reduced exposure products (PREP) for 6 weeks, I showed that gene expression differences induced by switching to PREP may only constitute a partially reduced exposure relative to smoking cessation. My results demonstrate that the nasal-epithelium can also serve as a minimally-invasive site to measure the responses to PREP and may ultimately yield biomarkers to evaluate the potential disease risks associated with these products.
Lastly, using small RNA-seq data from bronchial epithelial cells of smokers, I found alterations in airway micro-RNA expression that associate with time since quitting in former smokers.
These studies have provided novel insights into the physiologic responses of the airway epithelium to tobacco smoke and PREP and may ultimately serve as a useful approach for evaluating the disease risks associated with changes in smoking behavior. This work sets the stage for additional studies aimed at identifying prevention strategies that decrease the persistent risk of smoking-related lung disease in former smokers and identify biomarkers to assess lung disease risk in former smokers.